Radioisotopes

PET and SPECT owe their metabolic imaging ability to the radioisotopes that are used during the scans. Without actual tissue sampling, which is precluded in human subjects, localizing the injected metabolite is impossible. Since biological tissue is transparent to high energy photons, it makes sense to use them as beacons pointing to the location of the injected compound.

While SPECT uses gamma-emitting isotopes, PET uses positron-emmitting isotopes. The two most common ones are fluorine-18 and carbon-11.

Common Isotopes Used in PET

Isotope

Half-life

Maximum Energy (MeV)

Range in water (mm)

18F

109.7 min

0.635

2.39

11C

20.4 min

0.96

4.11

13N

9.96 min

1.19

5.39

15O

2.07 min

1.72

8.2

In the nucleus of each of these isotopes a proton decays into a neutron and a positron, as well as an electron neutrino. This reaction is forbidden for free protons, but can occur in the nucleus when the p-n binding energy is sufficiently different. As the positron leaves the nucleus, it comes to rest and annihilates with an electron to form two photons.

There are many different ways of producing these isotopes. For example 18O(p,n)18F and 13C(p,n)13N, with the notation a(b,c)d standing for a+b -> d+c. A cyclotron is used to accelerate the required particle which is then placed incident on a chemical target to produce the final isotope.

The rapid expansion of PET has been facilitated by two developments related to the production of radionuclides. The first was the development of the negative ion cyclotron and the second was the establishment of proton-only cyclotrons using enriched targets.

In the early 1960's the principle of accelerating negative hydrogen ions by extracting the protons by electron stripping was demonstrated. The potential for very high efficiency extraction with variable energy was realized shortly thereafter at UCLA and the University of Manitoba. In the mid 1970's, the TRIUMF 500 MeV H- cyclotron demonstrated the simultaneous extraction of two beams of varying energy using electron stripping of the negative ions.

It was not until a powerful small internal ion source was developed by The Cyclotron Corporation (TCC) that this technology could be applied to smaller cyclotrons designed for radioisotope production. The first in a series of negative ion cyclotrons was built by TCC and are known as CP42 (45) cyclotrons. There are a number of these machines around the world dedicated to the production of radioisotopes and radiotherapy. These machines can extract up to 200�A of protons. The Nordion International Incorporated machine at the TRIUMF site routinely produces over 20 mAh of beam on target per week.

The UBC PET group uses the EPCO TR-13 13 MeV cyclotron, which was designed and built through a collaboration and technology transfer agreement between TRIUMF and EBCO Technologies of Richmond, B.C. It accelerates H- ions which are then passed through a foil to strip away the electrons, leaving high energy protons. There is capacity for two 13 MeV beams at a current of 50μA each. There is a 4 target changer on each beam line. The beams are made to strike either a N2/H2 target for 11C, by way of the reaction 14N(p,a)11C, or an 18O2 target forming 18F by the process 18O(p,n)18F. The compounds that are produced are 11CH4, which is labeled methane, or 18F2, elemental fluorine. Production of 11C usually takes around 20 minutes. Because 18F has a longer half-life, it takes longer to produce the same amount of activity and production runs last about an hour.

Isotopes used for PET have these characteristics:

They have half-lives long enough to carry out scan but not too long as to expose the patient to an unnecessary radiation burden. Furthermore, the four isotopes listed in the table above provide a wide range of half-lives, providing flexibility in tracer design.

The decay positrons are relatively of low energy and therefore have short ranges in the body. The range is the distance which the positron travels before annihilating with the electron. This effect produces an inherent error in the data collected by the scanner and cannot be corrected.

High specific activities can be produced.

The targets are easily available for the production of all PET isotopes.

The isotopes are either (i) identical to the compounds found in the body or (ii) very similar in size in the case of 18F so that the labeled tracers are virtually identical to their non-labeled counterparts.